Cajal bodies shape genome conformation

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Authors

• IA Sawyer
• M-H Sung
• D Sturgill
• Q Wang
• SP Shevtsov
• G Pegoraro
• S Baek
• GH Hager
• M Dundr

Abstract

The Cajal body (CB) has been described as a reactionary, passive region which catalyzes the biogenesis of small nucle(o)lar RNAs (sn(o)RNAs) and recycling of essential spliceosomal components after splicing. This domain, which is primarily found in aneuploid transformed cells, is known to specifically form at sites of sn(o)RNA transcription and has been observed to interact with several classes of sn(o)RNA genes. Here, we examined the non-random positioning of CBs and their role in genome organization. Specifically, we examined clustering and regulation of sn(o)RNA genes by CBs, as well as histone genes through the physically associated Histone locus body. We find that CBs are predominantly located at the interface of multiple chromosomes. Genome-wide chromatin conformation capture analysis (4C-seq) revealed that CB-proximal regions are enriched in all categories of sn(o)RNA loci and histone gene loci. CB-associated genes form inter-chromosomal gene clusters in the 3D space. Analysis of the CB associated with chromosome 1 showed that the CB is necessary for configuring the entire chromosome into a rosette-like structure which envelopes the CB. RNAi-mediated disassembly of CBs leads to a substantial disruption of the CB-targeting gene clusters and suppression of sn(o)RNA and histone genes. We also observed a global increase in splicing noise even outside of the CB-proximal genomic regions. We conclude that CBs are not passive byproducts of specific gene activity, but play an active role in organizing the genome in 3D. This provides an optimized environment which accelerates sn(o)RNA processing and influences the maturation of RNA pol II-driven genes.

Scientific Focus Area: Chromosome Biology

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